Opioids are sometimes the subject of abuse. An opioid dosage can be concentrated in a solution to be consumed by oral ingestion, by injection, or transmucally via the anus. In a tablet form, it can be crushed into a powder for snorting (nasally).
A number of opioids are combination drugs containing not only an opioid such as oxycodone, but also an analgesic such as acetaminophen. To abuse these combination drugs, it is necessary for the abuser to separate out the acetaminophen before concentrating the opioid, because high dosages of this analgesic can cause liver damage. The separation method is called “cold water extraction,” and it uses the differences in solubility of oxycodone and acetaminophen to separate the two actives. The first step of this method is to dissolve multiple dosages in a small amount (5.0 mL) of warm water. The second step is to chill the solution, causing the less-soluble acetaminophen to precipitate out and be removed by filtration. A way of hindering the cold water extraction process is adding a gelling agent to the dosage, so that when water is added to the dosage, a gel is formed which holds the acetaminophen and the oxycodone together. Subsequently, they cannot be separated by filtration.
A number of additional approaches are known in the art for creating tamper-resistant forms of opioids, including using adversive agents (irritants, bitter and sour flavorings), opioid antagonists, opioid quenching agents, and covalently binding the opioid to amino acids.
Tamper-resistant delivery systems using gelling agents in a drug delivery form with the opioid are known in the art. When the dosage is dissolved in a small amount of water, instead of a solution, a viscous gel that cannot be injected may be formed. For combination drug systems, the gel prevents the acetaminophen from being removed by cold water extraction, because the gel retains the drugs together when extraction is attempted. U.S. Pat. Nos. 3,980,766 and 4,070,494 and U.S. patent application publications 2003/0068471, 2003/0068375, and 2007/0014732 disclose the use of gelling agents to create tamper-resistant drug delivery forms.
However, for each of these patents and publications, rapid gelling in combination with release of the opioid from the delivery system when ingested is not demonstrated, with the exception of U.S. Pat. No. 4,070,494. This patent discloses the use of a gelling agent with an opioid, and uses a “tail flick test” with rats to demonstrate release of the opioid. However, such release results are contrary to the data of the present application. Further, publications 2007/0014732 and 2003/0068471 found the use of gelling agents did not adversely affect release of the opioid, but the amount of gel added was very low, from 2.4 to 7.2% of the formula, and, according to their specifications, did not provide rapid gelling at those levels when tested, or gelling at all unless the mixture was heated, then cooled. The other patents and publications did provide gelling agents at a high enough concentration to cause rapid gelling, but did not address the problem of drug release upon ingestion.
The present application discloses that gelling agents can adversely affect the release of the opioid upon ingestion, thereby defeating the usefulness of the medication. However, the combination of an effective amount of gelling agent with a lipid suspension can provide both the desired rapid gelling in the presence of an aqueous solvent and the desired release of the drug in the digestive system.